Single-cell epigenetic profiling reveals an interferon response-high program associated with deficiency in kidney cancer.

Renal cell carcinoma (RCC) is characterized by recurrent somatic mutations in epigenetic regulators, which stratify patients into clinically significant subgroups with distinct prognoses and treatment responses. However, the cell type-specific epigenetic landscape of RCC-broadly and in the context of these mutations-is incompletely understood. To investigate these open questions, we integrated single nucleus ATAC sequencing data from RCC tumors across four independent cohorts.

Long interspersed nuclear elements safeguard neural progenitors from precocious differentiation.

Long interspersed nuclear element-1 (L1 or LINE-1) is a highly abundant mobile genetic element in both humans and mice, comprising almost 20% of each genome. L1s are silenced by several mechanisms, as their uncontrolled expression has the potential to induce genomic instability. However, L1s are paradoxically expressed at high levels in differentiating neural progenitor cells.

Signatures of a surface spin-orbital chiral metal.

The relation between crystal symmetries, electron correlations and electronic structure steers the formation of a large array of unconventional phases of matter, including magneto-electric loop currents and chiral magnetism. The detection of such hidden orders is an important goal in condensed-matter physics. However, until now, non-standard forms of magnetism with chiral electronic ordering have been difficult to detect experimentally.

Multiple-current states in a multicomponent superconducting channel.

It is well-established that multicomponent superconductors can host different nonstandard phenomena such as broken-time reversal symmetry (BTRS) states, exotic Fulde-Ferrell-Larkin-Ovchinnikov phases, the fractional Josephson effect as well as plenty of topological defects like phase solitons, domain walls and unusual vortex structures. We show that in the case of a two-component superconducting quasi-one-dimensional channel this catalogue can be extended by a novel inhomogeneous current state, which we have termed as a multiple-state, characterized by the coexistence of two different interpenetrating Cooper pair condensates with different total momenta. Within the Ginzburg-Landau formalism for a dirty two-band superconductor with sizable impurity scattering treated in the Born-approximation we reveal that under certain conditions, the occurrence of multiple-states can induce a cascade of transitions involving switching between them and the homogeneous BTRS (non-BTRS) states and vice versa leading this way to a complex interplay of homogeneous and inhomogeneous current states.

Pattern Formation by Electric-Field Quench in a Mott Crystal.

The control of the Mott phase is intertwined with the spatial reorganization of the electronic states. Out-of-equilibrium driving forces typically lead to electronic patterns that are absent at equilibrium, whose nature is however often elusive. Here, we unveil a nanoscale pattern formation in the CaRuO Mott insulator.

Structural and functional properties of mSWI/SNF chromatin remodeling complexes revealed through single-cell perturbation screens.

The mammalian SWI/SNF (mSWI/SNF or BAF) family of chromatin remodeling complexes play critical roles in regulating DNA accessibility and gene expression. The three final-form subcomplexes-cBAF, PBAF, and ncBAF-are distinct in biochemical componentry, chromatin targeting, and roles in disease; however, the contributions of their constituent subunits to gene expression remain incompletely defined. Here, we performed Perturb-seq-based CRISPR-Cas9 knockout screens targeting mSWI/SNF subunits individually and in select combinations, followed by single-cell RNA-seq and SHARE-seq.

Designing spin and orbital sources of Berry curvature at oxide interfaces.

Quantum materials can display physical phenomena rooted in the geometry of electronic wavefunctions. The corresponding geometric tensor is characterized by an emergent field known as the Berry curvature (BC). Large BCs typically arise when electronic states with different spin, orbital or sublattice quantum numbers hybridize at finite crystal momentum.

Gate Control of the Current-Flux Relation of a Josephson Quantum Interferometer Based on Proximitized Metallic Nanojuntions.

We demonstrate an Al superconducting quantum interference device in which the Josephson junctions are implemented through gate-controlled proximity Cu mesoscopic weak links. This specific kind of metallic weak links behaves analogously to genuine superconducting metals in terms of the response to electrostatic gating and provides a good performance in terms of current-modulation visibility. We show that through the application of a static gate voltage we can modify the interferometer current-flux relation in a fashion that seems compatible with the introduction of π-channels within the gated weak link.

Guiding antiferromagnetic transitions in Ca[Formula: see text]RuO[Formula: see text].

Understanding and controlling the transition between antiferromagnetic states having different symmetry content with respect to time-inversion and space-group operations are fundamental challenges for the design of magnetic phases with topologically nontrivial character. Here, we consider a paradigmatic antiferromagnetic oxide insulator, Ca[Formula: see text]RuO[Formula: see text], with symmetrically distinct magnetic ground states and unveil a novel path to guide the transition between them. The magnetic changeover results from structural and orbital reconstruction at the transition metal site that in turn arise as a consequence of substitutional doping.

Colossal Orbital Edelstein Effect in Noncentrosymmetric Superconductors.

In superconductors that lack inversion symmetry, the flow of supercurrent can induce a nonvanishing magnetization, a phenomenon which is at the heart of nondissipative magnetoelectric effects, also known as Edelstein effects. For electrons carrying spin and orbital moments, a question of fundamental relevance deals with the orbital nature of magnetoelectric effects in conventional spin-singlet superconductors with Rashba coupling. Remarkably, we find that the supercurrent-induced orbital magnetization is more than 1 order of magnitude greater than that due to the spin, giving rise to a colossal magnetoelectric effect.

knockout in excitatory neurons impairs postnatal synapse maturation and increases the repressive histone modification H3K27me3.

Two epigenetic pathways of transcriptional repression, DNA methylation and polycomb repressive complex 2 (PRC2), are known to regulate neuronal development and function. However, their respective contributions to brain maturation are unknown. We found that conditional loss of the de novo DNA methyltransferase in mouse excitatory neurons altered expression of synapse-related genes, stunted synapse maturation, and impaired working memory and social interest.

Single-nucleus cross-tissue molecular reference maps toward understanding disease gene function.

Understanding gene function and regulation in homeostasis and disease requires knowledge of the cellular and tissue contexts in which genes are expressed. Here, we applied four single-nucleus RNA sequencing methods to eight diverse, archived, frozen tissue types from 16 donors and 25 samples, generating a cross-tissue atlas of 209,126 nuclei profiles, which we integrated across tissues, donors, and laboratory methods with a conditional variational autoencoder. Using the resulting cross-tissue atlas, we highlight shared and tissue-specific features of tissue-resident cell populations; identify cell types that might contribute to neuromuscular, metabolic, and immune components of monogenic diseases and the biological processes involved in their pathology; and determine cell types and gene modules that might underlie disease mechanisms for complex traits analyzed by genome-wide association studies.

Unveiling unconventional magnetism at the surface of SrRuO.

Materials with strongly correlated electrons often exhibit interesting physical properties. An example of these materials is the layered oxide perovskite SrRuO, which has been intensively investigated due to its unusual properties. Whilst the debate on the symmetry of the superconducting state in SrRuO is still ongoing, a deeper understanding of the SrRuO normal state appears crucial as this is the background in which electron pairing occurs.

Coupling Charge and Topological Reconstructions at Polar Oxide Interfaces.

In oxide heterostructures, different materials are integrated into a single artificial crystal, resulting in a breaking of inversion symmetry across the heterointerfaces. A notable example is the interface between polar and nonpolar materials, where valence discontinuities lead to otherwise inaccessible charge and spin states. This approach paved the way for the discovery of numerous unconventional properties absent in the bulk constituents.

Conventional type I dendritic cells maintain a reservoir of proliferative tumor-antigen specific TCF-1 CD8 T cells in tumor-draining lymph nodes.

In tumors, a subset of CD8 T cells expressing the transcription factor TCF-1 drives the response to immune checkpoint blockade. We examined the mechanisms that maintain these cells in an autochthonous model of lung adenocarcinoma. Longitudinal sampling and single-cell sequencing of tumor-antigen specific TCF-1 CD8 T cells revealed that while intratumoral TCF-1 CD8 T cells acquired dysfunctional features and decreased in number as tumors progressed, TCF-1 CD8 T cell frequency in the tumor draining LN (dLN) remained stable.

Spatially organized multicellular immune hubs in human colorectal cancer.

Immune responses to cancer are highly variable, with mismatch repair-deficient (MMRd) tumors exhibiting more anti-tumor immunity than mismatch repair-proficient (MMRp) tumors. To understand the rules governing these varied responses, we transcriptionally profiled 371,223 cells from colorectal tumors and adjacent normal tissues of 28 MMRp and 34 MMRd individuals. Analysis of 88 cell subsets and their 204 associated gene expression programs revealed extensive transcriptional and spatial remodeling across tumors.

Introduction of the neonatal sepsis calculator at a low-dependency special care nursery in Australia.

Background: The neonatal early onset sepsis calculator (Sepsis Calculator) is a screening tool for managing neonates at risk of early onset sepsis (EOS). In large tertiary centers it has been found to reduce empiric antibiotic use in newborns with suspected EOS by up to half, without missing EOS confirmed by blood culture.

Aims: To evaluate the effect of implementation of the Sepsis Calculator at a low-dependency special care nursery in Australia on rates of antibiotic treatment for suspected EOS in newborns, and, to determine the compliance rate in applying the Sepsis Calculator.

Blockade of IL-22 signaling reverses erythroid dysfunction in stress-induced anemias.

Patients with myelodysplastic syndromes (MDSs) display severe anemia but the mechanisms underlying this phenotype are incompletely understood. Right open-reading-frame kinase 2 (RIOK2) encodes a protein kinase located at 5q15, a region frequently lost in patients with MDS del(5q). Here we show that hematopoietic cell-specific haploinsufficient deletion of Riok2 (Riok2Vav1) led to reduced erythroid precursor frequency leading to anemia.

Tumor and immune reprogramming during immunotherapy in advanced renal cell carcinoma.

Immune checkpoint blockade (ICB) results in durable disease control in a subset of patients with advanced renal cell carcinoma (RCC), but mechanisms driving resistance are poorly understood. We characterize the single-cell transcriptomes of cancer and immune cells from metastatic RCC patients before or after ICB exposure. In responders, subsets of cytotoxic T cells express higher levels of co-inhibitory receptors and effector molecules.